Clinical Impression: This is almost certainly a Hereditary Motor and Sensory Neuropathy (HMSN) - most likely Charcot-Marie-Tooth Disease (CMT)

Why CMT fits so well

• Bilateral foot drop
• Distal-only neuropathy - glove-and-stocking pattern in both hands and both feet below the knee
• Non-progressive over 26 years
• Bilateral and symmetric

• Peroneal nerve distribution weakness causing ankle inversion/buckling - this is the classic first presentation of CMT
• Age 7, so within the first decade - CMT1A "usually presents in the first or early second decade of life as a slowly progressive distal demyelinating motor and sensory neuropathy with motor symptoms predominating" - Robbins PBD
• Nocturnal leg pains over the past year - a well-recognized prodromal/early symptom in CMT children, often dismissed as "growing pains," but in fact representing sensory nerve involvement

Differential to keep in mind: HNPP

• The child presents with a single, relatively acute peroneal mononeuropathy (2-3 months)
• HNPP is caused by deletion of PMP22 (the reciprocal of the CMT1A duplication)
• It presents with recurrent, episodic, pressure-sensitive mononeuropathies - the peroneal nerve at the fibular head is one of the most common sites
• Frameworks for Internal Medicine describes: "recurrent episodes of bilateral lower extremity weakness and numbness that usually occur after periods of prolonged sitting"

Summary of the Two Most Likely Diagnoses

What you should do / recommend as a physiotherapist

• The child needs a pediatric neurologist or neuromuscular specialist
• Investigations needed: nerve conduction studies (NCS/EMG) in both the child and father; genetic testing for PMP22 duplication/deletion
• If father hasn't been genetically confirmed, this case presents a perfect opportunity for the whole family to get tested

• Do NOT perform aggressive stretching, weight-bearing exercises on the peroneal nerve, or deep cross-friction massage at the fibular head area - if this is HNPP, pressure and traction worsen nerve injury
• Address the ankle inversion / foot drop with gentle dorsiflexion muscle strengthening (tibialis anterior, peronei)
• Ankle-foot orthosis (AFO) - this is first-line for functional foot drop in CMT children; prevents falls, supports gait, and may reduce progressive deformity
• Stretching of the Achilles tendon / plantar fascia - pes cavus is a common secondary deformity in CMT; early stretching and night splinting can delay its evolution
• Balance and proprioceptive training - CMT children have significant balance deficits due to combined motor and sensory loss
• Avoid prolonged compression at the fibular head (avoid sitting with legs crossed, kneeling for long periods) - relevant whether it is CMT or HNPP

Bottom Line

Robbins Pathologic Basis of Disease: CMT1A "usually presents in the first or early second decade of life as a slowly progressive distal demyelinating motor and sensory neuropathy" | Bradley and Daroff's Neurology: In HNPP, "the primary treatment strategy is to prevent nerve injury by avoiding pressure damage"

What to Expect if This is CMT - The Natural History

Phase 1 - What's Already Happening (Age 5-10)

• Peroneal weakness - foot drop, ankle instability, tendency to invert - she is already here
• Night leg pains / cramps - sensory nerve irritation before frank sensory loss - she already had this
• Clumsiness, slow running, poor balance - often dismissed as "just the way the child is"
• Absent or reduced ankle deep tendon reflexes - check this; it's an early sign
• Deep tendon reflexes at the knee are typically preserved at this stage

Phase 2 - Foot and Gait Deformity Develops (Over the Next 5-10 Years)

• Pes cavus (high arch) - as the intrinsic foot muscles weaken, the arch rises. In a growing child this becomes structural and fixed over time
• Hammer toes / claw toes - imbalance between intrinsic (weak) and extrinsic toe flexors
• Steppage gait - she compensates for foot drop by exaggerated hip/knee flexion to clear the foot
• Recurrent ankle sprains - due to peroneal weakness, poor proprioception, and cavovarus deformity
• Metatarsalgia / pain under the ball of the foot - callus formation from abnormal weight distribution

Phase 3 - The "Inverted Champagne Bottle" Legs (Adolescence to Early Adulthood)

• Distal leg muscle atrophy - the classic appearance. Thighs remain normal, calves and shin muscles waste away giving the characteristic "stork leg" or "inverted champagne bottle" shape
• Weakness creeps proximally - from ankle dorsiflexors up to the lower leg, eventually the thighs
• Ankle-foot orthoses (AFOs) become necessary - Goldman-Cecil Medicine states: "Ankle-foot orthoses are frequently required by the third decade"
• Falls increase - balance is compromised by both motor weakness and sensory loss (vibration and proprioception go first)

Phase 4 - Upper Limb Involvement (Late Adolescence / Adulthood)

• Intrinsic hand muscle weakness - fine motor difficulties: fastening buttons, zippers, jewelry, writing, turning keys
• Distal hand/forearm atrophy
• Sensory loss in hands - the father already has this (glove distribution)
• Goldman-Cecil notes specifically: "Fine hand movements such as fastening jewelry, turning a key, or using buttons and zippers may be impaired"

What About Prognosis? (The Good News for CMT1A Specifically)

Other Things to Watch For

• Scoliosis - occurs in a subset of CMT children, especially during the growth spurt. Screen for it annually
• Hip dysplasia - less common, but reported
• Hearing loss - rare, seen in some CMT subtypes (CMTX, certain CMT1 mutations)
• Fatigue - a very real and often underappreciated symptom; children tire easily over long distances (school corridors, malls) due to the extra energy cost of compensated gait
• Respiratory involvement - extremely rare in CMT1A, more a concern in severe axonal forms

The Father's Course as Your Prognostic Guide

• AFOs long-term
• Likely foot surgery at some point (tendon transfer, plantar fasciotomy, osteotomy for pes cavus correction) - typically in the teenage years if deformity is structural
• Ongoing physiotherapy throughout life for strengthening, balance, and functional training
• Possible hand therapy when upper limb involvement begins
• Annual monitoring for scoliosis, gait change, and new functional losses

Your Key Monitoring Parameters as a Physiotherapist

1. Ankle dorsiflexion range (passive and active)
2. Peroneal muscle strength (manual muscle test)
3. Heel-rise test - calf strength indicator
4. Foot posture index - early pes cavus detection
5. Balance - single leg stance, functional reach
6. Gait analysis - steppage gait, trunk compensations
7. Timed 10-meter walk / 6-minute walk for longitudinal comparison
8. Hand grip and pinch strength - as she gets older

Sources: Goldman-Cecil Medicine 26th Ed; Campbell's Operative Orthopaedics 2026; Robbins Pathologic Basis of Disease; Multidisciplinary CMT Management Review, PMC

What to Expect if CMT - Summary

Near Term (she's already in this phase)

• Peroneal weakness / ankle instability - already present
• Night leg cramps / sensory discomfort - already present
• Absent ankle deep tendon reflexes - check this now
• Clumsiness, slow running, poor balance

Over the Next 5-10 Years (childhood into adolescence)

• Pes cavus (high arch develops and becomes fixed as she grows)
• Claw/hammer toes
• Steppage gait worsens
• Recurrent ankle sprains from peroneal weakness + poor proprioception
• Distal leg muscle atrophy - the classic "inverted champagne bottle" / stork leg appearance
• AFO likely needed by her teens (Goldman-Cecil states: "ankle-foot orthoses are frequently required by the third decade")

Later (adolescence into adulthood)

• Fine hand motor difficulty - buttons, zippers, writing, keys
• Distal hand/forearm atrophy - as the father already has
• Falls risk increases - due to combined motor + sensory (proprioception) loss
• Watch for scoliosis during growth spurts - screen annually
• Fatigue with walking long distances is real and underappreciated

Prognosis - The Reassuring Part

1. Warts - as in plantar warts or verrucae (relevant to CMT foot care)?
2. WARS1 - a gene associated with a CMT subtype (glycyl/tryptophanyl-tRNA synthetase)?
3. Something completely different - a topic change to World War 1?
4. A continuation of the CMT discussion - perhaps "What are the Stage 1" findings?

WARS1 Heterozygous - What This Means for the Child

What is WARS1?

• OMIM #617721
• Inheritance: Autosomal dominant - one mutant copy is sufficient to cause disease
• The seminal paper (Tsai et al., Brain 2017) established WARS as a cause of autosomal dominant distal hereditary motor neuropathy (dHMN type IX)
• The mechanism is a dominant-negative effect on aminoacylation activity - it is NOT simple haploinsufficiency, meaning the mutant protein actively interferes with the normal copy

The Key Clinical Distinction: This is a Distal Hereditary Motor Neuropathy (dHMN), not classical CMT

What to Expect in This 7-Year-Old

• She will have progressive distal limb weakness - feet and legs first, hands later
• Sensory loss will be minimal - this is different from classic CMT
• This means her proprioception and balance may be relatively better preserved initially compared to CMT1A
• But motor weakness and atrophy will be the dominant problem

• Father's onset was in adolescence/adulthood (the family paper shows onset 15-23 years)
• This child is presenting at age 7 which is earlier than typical - watch her carefully
• Early onset can sometimes signal a slightly more severe phenotype, though intrafamilial variability is well documented in ARS neuropathies

• Axonal pattern - reduced compound muscle action potential (CMAP) amplitude, relatively preserved nerve conduction velocity (NCV >38 m/s)
• Sensory nerve action potentials (SNAPs) relatively preserved or only mildly reduced
• This is the NCS signature of dHMN / CMT2, not the slow-velocity demyelinating pattern of CMT1A

• Father's 26-year non-progressive stable course is the best prognostic guide
• WARS1 dHMN tends to be slowly progressive and relatively mild to moderate
• Most patients maintain ambulation throughout life
• The Tsai et al. Brain 2017 cohort showed the mutation causes distal limb weakness and atrophy with a relatively mild functional course

• Progressive peroneal and tibial muscle weakness - foot drop will worsen unless managed
• Intrinsic foot muscle atrophy - pes cavus may develop but may be less severe than in demyelinating CMT
• Steppage gait worsening
• Eventually hand intrinsic muscle weakness - fine motor tasks
• No significant sensory loss expected - this is actually reassuring for balance, pressure sore risk, and quality of life

Critical Point: Biallelic vs. Heterozygous WARS1

• Heterozygous (what father and child have): dominant dHMN - motor neuropathy, generally milder, compatible with active life
• Biallelic / homozygous WARS1 (different!): causes a severe neurodevelopmental syndrome with intellectual disability, hearing impairment, microcephaly, and brain abnormalities (Lin et al. Hum Mutat 2022, PMID 35815345)

Implications for Your Physiotherapy Management

1. Sensory testing is still important - even though sensory loss is minimal, check vibration and proprioception at every visit; any sensory decline warrants urgent neurological review
2. Motor strength monitoring is your primary metric - manual muscle testing of tibialis anterior, peronei, intrinsics, toe extensors at every session
3. AFO is still indicated - foot drop is motor-driven; AFO will prevent falls and compensatory gait deformities
4. Strengthening exercises are appropriate and beneficial - since this is axonal/motor, strengthening programmes are well tolerated in dHMN (unlike demyelinating forms where over-fatigue is a concern)
5. Less risk of pressure sores / insensate foot compared to classic CMT - she retains sensation, so standard orthotics are safer and she can give feedback on fit
6. Genetic counselling for the family - autosomal dominant means each child of an affected parent has a 50% chance of inheriting the variant. If there are siblings, they should be assessed

What the Father's Stable Course Tells You

Key references: Tsai et al., Brain 2017 (PMID 28369220) - foundational WARS paper; Wang et al., Clin Genet 2019 (PMID 31069783) - confirmed mild-moderate phenotype; Lin et al., Hum Mutat 2022 (PMID 35815345) - biallelic vs heterozygous distinction